The topic of the present study is the accumulation of new information regarding the structural modification of DNA associated with carcinogen interaction. A few model systems have been established to analyze the conformational changes in double-stranded circular DNA (pBR322 plasmid and SV40 virus) resulting from covalent and noncovalent binding of benzo(a)pyrene metabolites and mutagenic amino acid pyrolysates, dehydration by organic solvents, temperature change, polyamines and salts. The results indicate that the helical structure of DNA changes specifically under different physico-chemical conditions. Perturbation of the water activity around DNA and the consequent structural transformation may change the binding efficiency as well as binding specificity of the carcinogens. Such microenvironmental changes are expected to occur physiologically in living cells. Alteration of target sites is dependent not only on the chemistry of carcinogens but is also influenced by DNA structure.